Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epigallocatechin gallate (EGCG) is the most abundant and effective green tea catechin and has been reported to attenuate diabetic nephropathy (DN). However, the mechanism by which EGCG ameliorates DN, till now, has remained unclear. EGCG is known as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defense against diabetes-induced oxidative stress and in the prevention of DN. In the present study, we tested whether NRF2 is required for EGCG protection against DN. Therefore, C57BL/6 wild type (WT) and Nrf2 knockout mice were induced to diabetes by streptozotocin, in the presence or absence of a 24-week treatment with EGCG. In the WT mice, EGCG activated Nrf2 expression and function without altering the expression of Kelch-like ECH-associated protein 1 (Keap1). Diabetes-induced renal oxidative damage, inflammation, fibrosis and albuminuria were significantly prevented by EGCG. Notably, deletion of the Nrf2 gene completely abrogated these actions of EGCG. To further determine the effect of EGCG on KEAP1/NRF2 signaling, mouse mesangial cells were treated with high glucose, in the presence of both Keap1 siRNA and EGCG. Interestingly, EGCG failed to enhance NRF2 signaling and alleviate oxidative, inflammatory and fibrotic indicators, in the presence of Keap1 siRNA. The present study demonstrated, for the first time, that NRF2 plays a critical role in EGCG protection against DN. Other findings indicated that inactivation of KEAP1 protein by EGCG may mediate EGCG function in activating NRF2.
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PMID:Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1. 2845 36

Macrovascular complications develop in over a half of the diabetic individuals, resulting in high morbidity and mortality. This poses a severe threat to public health and a heavy burden to social economy. It is therefore important to develop effective approaches to prevent or slow down the pathogenesis and progression of macrovascular complications of diabetes (MCD). Oxidative stress is a major contributor to MCD. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) governs cellular antioxidant defence system by activating the transcription of various antioxidant genes, combating diabetes-induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch-like ECH-associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of the Nfe2l2 gene transcription, decreasing KEAP1 protein level by microRNA-induced degradation of Keap1 mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in prevention of MCD. This review provides a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review.
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PMID:Protective role of NRF2 in macrovascular complications of diabetes. 3262 15